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E-MTAB-7221

ABSTRACT: Global transcriptomic profiles of blood monocytes from Hmox1 homozygous knockout mice compared to wild type controls following Mtb infection

PROVIDER: E-MTAB-7221 | ExpressionAtlas | 2020-01-28

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-MTAB-7221-analysis-methods.tsv	Tabular
	E-MTAB-7221-atlasExperimentSummary.Rdata	Rdata
	E-MTAB-7221-configuration.xml	Xml
	E-MTAB-7221-percentile-ranks.tsv	Tabular
	E-MTAB-7221.condensed-sdrf.tsv	Tabular

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Project description:Blood CD14+ monocytes are the frontline immunomodulators categorized into classical, intermediate or non-classical subsets, subsequently differentiating into M1 pro- or M2 anti-inflammatory macrophages upon stimulation. While Zika virus (ZIKV) rapidly establishes viremia, the target cells and immune responses, particularly during pregnancy, remain elusive. Furthermore, it is unknown whether African- and Asian-lineage ZIKV have different phenotypic impacts on host immune responses. Using human blood infection, we identified CD14+ monocytes as the primary target for African- or Asian-lineage ZIKV infection. When immunoprofiles of human blood infected with ZIKV were compared, a classical/intermediate monocyte-mediated M1-skewed inflammation by African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by Asian-lineage ZIKV infection. Importantly, infection of pregnant women’s blood revealed enhanced susceptibility to ZIKV infection. Specifically, Asian-lineage ZIKV infection of pregnant women’s blood led to an exacerbated M2-skewed immunosuppression of non-classical monocytes in conjunction with global suppression of type I interferon-signaling pathway and an aberrant expression of host genes associated with pregnancy complications. 30 ZIKV+ sera from symptomatic pregnant patients also showed elevated levels of M2-skewed immunosuppressive cytokines and pregnancy complication-associated fibronectin-1. This study demonstrates the differential immunomodulatory responses of blood monocytes, particularly during pregnancy, upon infection with different lineages of ZIKV.

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Global transcriptomic profiles of blood monocytes from Hmox1 homozygous knockout mice compared to wild type controls following Mtb infection

Project description:Since whole blood transcriptome profiling has been proposed as a reliable measure of immune responses in TB patients and because the plasma levels of HO-1 have been suggested as a potential TB diagnostic marker, we wanted to see the differences in the global transcriptomic profiles and the downstream pathways in the blood monocytes isolated from Mtb-infected HO-1 Wt and KO mice.

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In vivo single-cell and bulk transcriptomics reveals murine Leishmania major infection drives a pro-inflammatory signature alongside a signature of decreased ribosomal biogenesis.

Project description:Leishmania parasites cause cutaneous leishmanina (CL), a pathologic disease characterized by disfiguring, ulcerative skin lesions. Both parasite and host gene expression following infection with various Leishmania species has been investigated in vitro, but global transcriptional analysis following L. major infection in vivo is lacking. Thus, we conducted a comprehensive transcriptomic profiling study combining bulk RNA sequencing and single-cell RNA sequencing (scRNA-Seq) to identify global changes in gene expression in vivo following L. major infection. Bulk RNA-Seq analysis revealed that host immune response pathways like the antigen processing and presentation pathway were significantly enriched amongst differentially expressed genes (DEGs) upon infection, while ribosomal pathways were significantly downregulated in infected mice compared to naive controls. scRNA-Seq analyses revealed cellular heterogeneity including distince resident and recruitment cell types in the skin following L. major infection. Within the individual immune cell types, several DEGs indicative of many interferon induced GTPases and antigen presentation molecules were significantly enhanced in the infected ears including macrophages (H2-K1, H2-D1, Gbp4, Gbp8, Gbp2), and inflammatory monocytes (Gbp2, Gbp5, Gbp7, Gbp3). Ingenuity Pathway Analysis of scRNA-Seq data indicated the antigen presentation pathway was increased with infection, while EIF2 signaling is the top downregulated pathway followed by eIF4/p70S6k and mTOR signaling in multiple cell types including macrophages, BECs, and LECs. Altogether, this transcriptomic profile highlights known recruitment of myeloid cells to lesions and recognizes a previously undefined role for EIF2 signaling in murine L. major infection in vivo.

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